Substituted piperidinium chlorides

ABSTRACT

Incapacitating agents wherein heterocyclic substituents are attached to the 1-position of the piperidine and methods of producing same comprising reacting a substituted acetyl, secondary amine and formaldehyde in an alcohol with subsequent treatment forming the iodide salt which is further reacted with 4-phenyl-4-piperidinol forming the corresponding N-substituted piperidinol. The latter piperidinol is treated with propionyl chloride and acid producing the salt of the N-substituted 3-oxo alkyl derivative of piperidium chloride. The corresponding 3-hydroxy derivative of the said 3-oxo alkyl derivative is prepared by reacting the latter derivative with an alcoholic alkali metal borohydride.

United States Patent [191 Hydro SUBSTITUTED PlPERlDlNlUM CHLORIDES [75]Inventor: William R. Hydro. Bel Air. Md

[73] Assignee: The United States of America as represented by theSecretar 0f the Army. Washington DC.

221 Filed: Dec. l, I967 [21] Apple No.:687.392

[52] US. Cl. Hill/293.67; 260/29368; 414/267 [5 l] Int. Cl.'-' H C07D405/02 [58] Field of Search. 260/2943 A. 293.67, 293468;

[56] References Cited UNITED STATES PATENTS 3.408.356 lU/l968 HOI'O\l[Zi i a r .7 Ital/194.3

PI'iHltH' E.vmm'uerLeland A Sebastian Attorney. Agenl, or Firm-NathanEdelberg'. Robert P. Gibson; Kenneth P. Van Wyck 1 Nov. 11, 1975 [57}ABSTRACT lncapacitating agents wherein heteroqclic substituents areattached to the l-position of the piperidine and methods of producingsame comprising reacting a substituted acet \l. secondar) amine andformaldehyde in an alcohol with subsequent treatment forming the iodidesalt which is further reacted with 4-phen vl-4- piperidinol fomiing thecorresponding N-substituted piperidinol The latter piperidinol istreated with propion \'l chloride and acid producing the salt of the Nsubstituted 3-oxo alkyl derivative of piperidium chloride.

The corresponding 3-hydroxv derivative of the said 3 0m alkyl derivativeis prepared by reacting the latter derivative with an alcoholic alkalimetal borohydrider [2 Claims, N0 Drawings SUBSTITUTED PIPERIDINIUMCHLORIDES DEDICATORY CLAUSE The invention described herein may bemanufactured, used, and licensed by or for the Government forgovernmental purposes without the payment to me of any royalty thereon.

This invention relates to new N-substituted piperidine compounds andtheir method of preparation.

It is the object of the present invention to provide useful compositionsof novel heterocyclic substituents attached to the 1 position of thepiperidine ring.

It is a further object of the invention to provide compositions whichhave greater incapacitation levels than known compounds.

Piperidines are known as having a large number of aryl and lower acyloxysubstituents attached to the 4- position carbon atom of the piperidinering. Other groups substituted on piperidines are also known in whichvarious radicals are attached to the nitrogen atom of piperidine ringsuch as lower alkyl and aralkyl.

Carabateas et al., J. Med. P/larm. Chem, Vol 5, p. 913 (1962) published4-phenyl-4-propionoxy piperidines with various substituents attached tothe l-position. The substituents which were of particular interest werethe (3-hydroxy-3-phenylpropyl) and (3-oxo-3- phenylpropyl) since theirpotency relative to meperidine were 32l9 and 1346, respectively.

An investigation was instituted to prepare compounds with greaterpotency than have hitherto been prepared. The search for these compoundsfinally rested in the preparation of furan and thiophene derivatives of4-phenyl-4-propionoxy piperidines having the following structure:

wherein R is Z is lower alkylene of l to 4 carbon atoms compound A whereR is and Q is compound B where R is and Q is compound C where R is and Qis compound D where R is H ll 0 and Q is l have discovered that when thereaction products resulting from reacting about l0-25g of a substitutedacetyl, 6-15 g of a secondary amine, and 2-9g of formaldehyde in analkaline lower alkyl alcohol in the presence of methyl iodide formingthe iodide salt which is reacted with l-lOg of 4-phenyl-4-piperidinol toform the N-substituted 4-phenyl-4'piperidinol. The latter piperidinol istreated with 0.2-2.0g propionyl chloride and anhydrous hydrochloric acidproduced the N-substituted 3-oxo lower alkyl derivatives of thepiperidium chloride compounds of the invention. The correspondingN-substituted 3-hydroxy lower alkyl derivative is prepared by treating3-oxo derivative with about 0.16-0.20g of alkali metal borohydride andthen anhydrous hydrogen chloride and lower alkyl acetate gave rise tothe said N-substituted 3-hydroxy derivative.

The potency of these new compounds varies from about 0.2 to 8.0 times aseffective as l-[3-oxo-3- phenylpropyl]4-phenyl-4-acyloxy piperidinehydrochloride being the standard in Table l.

Pharmacological evaluation of the N-substituted piperidines of thisinvention for potency was determined by the administering intravenouslyvarious proportions (mg/kg) of the compounds upon mice using the methodof The Search for and Selection of Toxic Chemical Agents for WeaponsSystems" disclosed in the Edgewood Arsenal, Maryland Publication (CRDLSOP 70-3, May 6, 1965 LD is the lowest dose in mg of compound perkilogram of animal required to be lethal in 50% of the tested animals.MED- is the lowest dose in mg of compound per kilogram of animalrequired to give any visible physiological effects (i.e., mydriasis) in50% of the tested animals. The quotient of the ratio LD -,,,/MEDdescribed in Table 1 below is the margin of safety that is the highernumerical quotient the greater the proportion of agent can be usedbefore causing death and therefore a better incapacitating agent.

Table 1 Compound Potency (LD /M ED Standard 1 A 7.) B 2.8 C (1.23 D 5.0

Standard l-( 3-Oxy3-phenylpropyl )-4-phenyl-4-propionoxypiperidiniumChloride.

l-[ 3 -Oxy-3-( Z-thienyl )propyl1-4-phenyl-4-propionoxypiperidiniumChloride l-[ 3-Hydroxy-3-(Z-thienyl)propyl1-4-phenyl-4-propionoxypiperidinium Chloride.

l -[3-Oxy-3-(2-fury1)propyl]-4-phenyl-4-propionoxy piperidiniumChloride. Dl-[3-Hydroxy-3-(2-fury])propyl]-4-phenyl-4-propionoxypiperidiniumChloride.

The marked increase in incapacitation displayed by the compounds of thisinvention is very clear. While compound C may appear less desirable inexhibiting an approximate lower margin of safety, the compound isunmistakably a more effective lethal agent.

The inventor also contemplates the use of 4phenyl-4- acyloxypiperidines, such as are disclosed and their method of preparation inthe copending application, Ser. No. 648.546, filed June 21. 1967, toHydro and Sundberg, assignors to the US. Government, to be condensedwith Z-thienyl vinyl ketone as an alternate method to prepare thecompounds of this invention.

As the lower alkyl alcohol there may be used methanol, ethanol.propanol, isopropanol or butanol.

The ether employed can be methyl, ethyl, propyl, or butyl.

The alkaline agent may be any alkali metal hydroxide such as sodium orpotassium.

The molecular structures of the compounds of the invention areestablished by their synthesis and corroborated by the correspondence offactual material from the physical. calculated and found values for theelementary analyses and spectral analyses.

EXAMPLE 1 a. Z-(Z-ThenoyUethyl dimethylamine Hydrochloride An alcoholicsolution is prepared by refluxing on a steam bath for about 4 hours of amixture of about 20.0g of Z-acetylthiophene, 13.0g dimethylaminehydrochloride, 5.7g paraformaldehyde and 50.0 ml absolute alcohol andupon cooling a heavy white insoluble product is removed by filtrationand dried in an oven at 50C. for 2 hours. The dried product amounts toabout 17.3g, m.p. l7ll73C.

b. 2-(2-Thenoyl)ethyltrimethylammonium Iodide A suspension comprisingabout 16.3g of 2-(2- thenoyl)-ethyldimethylamine hydrochloride [see (a)above] in 350 ml water cooled in an ice bath is made basic with 4-8 mlof 35% sodium hydroxide solution forming an immiscible oily phase. Etherextracts are prepared by treating the isolated oily phase 3 times withl00 ml portions of ether and the combined extracts are dried overanhydrous sodium sulfate, filtered and refluxed on a steam bath forabout one-half hour to remove any dimethylamine. and subsequent additionin a dropwise manner over a /2-hour duration of an ether solutioncomprising of about 10.6g methyliodide in 50 ml of sodium-dried etherforms a white precipitate. The mixture is continued to be refluxed foran additional 1 to 2 hours after the ether-iodide addition. cooledovernight, and the white precipitate separated by filtration is washedwith sodium-dried ether and dried in a vacuum oven at 50C., a yield ofabout 17.3g, m.p. 202205C. decomposition.

c. l-[ 2-( 2-Thenoyl )ethyl ]-4-phenyl-4-piperidinol water A mixturecomprising about l6.0g of 2-(2-Thenoyl- )ethyltrimethylammonium Iodide.see (b) above, 8.7g. of 4-phenyl-4-piperidinol, 10.4g of sodiumcarbonate, and ml of dimethyl formamide is stirred at ambienttemperature with nitrogen bubbling through mixture for about 5 hours toexpel the formed trimethylamine, and pouring the stirred mixture into aliter of wataer forming an insoluble product and cooling the reactingmixture overnight. The insoluble product is removed, copiously washedwith distilled water and dried overnight at about 80C. The yield isabout 13.5g, m.p. l46l48C., recrystallization from benzene gave a m.p.148-l50C.

Anal. Calc. C,,,H ,NO S: C, 68,54; H, 6.71; S, 10.17. Found: C, 68.58;H, 6.45; S, 10.2.

d. l-[ 3-Oxo-3-( Z-thienyl )propyll-4-phenyl-4-propionoxypiperidiniumChloride At ambient temperatures, a chloroform solution comprising about1.8g propionyl chloride in 20 ml chloroform is added rapidly dropwise toa stirring mixture comprising about 13.5g sodium carbonate, 2.3g water,ml chloroform and 5.0g l-[2-(2-Thenoyl)- ethyl]-4-phenyl-4-piperidinol,see (c) above, with continued agitation for about 4-5 hours. Thechloroform mixture reaction product is filtered and the volatiles areremoved in vacuo in a rotary evaporator utilizing a minimum of heat toform a syrupy product which is dissolved in ether, dried over anhydrousmagnesium sulfate for about 1 hour and filtered. The ether solution iscooled from about S to +8C. and with stirring anhydrous hydrogenchloride is added until complete precipitation of the salt is obtained,whereupon the mixture is evaporated in vacuo in a rotary evaporator. Theresidue is triturated with ethyl acetate and cooled rapidly with theproduct isolated by filtration. The product is crystallized from acetoneor acetone-ether to give a yield of about 4.5g. m.p. l69l71C. Theproposed structure was confirmed by infrared spectrum.

Anal. Cale. C H -Cl N0 8: C, 61.83; H, 6.42; S. 7.86. Found: C, 61.48;H, 6.96, S. 7.97.

e. l-[ 3-Hydroxy 3-( Z-thienyl )propyl]-4-phenyl-4-propionoxypiperidinium Chloride A methanolic alkalinesolution comprises a sodium hydroxide pellet in 60 ml of methanol.

An approximate neutral alcoholic solution (pH 6.5 7.5) at about C.comprises about 1.5g of l-[3-Oxo- 3-( Z-thienyl )propyl]-4-phcnyl-4-propionoxypiperidinium chloride, see (d) above. in 50 ml at0C. of above prepared methanolic solution.

Sodium borohydride about (0.1 8g) is dissolved in the remaining l0 ml ofthe above prepared methanolic solution. filtered and added to the saidalcoholic solution (pH 6.57.5) over 8 to 10 minutes at about 0C. andmaintained at this temperature for an additional 6 hours. The reactedalcoholic mixture (clear, colorless solution. pH 8.5-9.5) is treatedwith anhydrous hydrochloric acid (about pH 2.0) with subsequent removalof volatiles in vacuo. The residue extracted with ethyl acetate.filtered and evaporated in vacuo yielded a white frothy solid product.The product is highly soluble in ethyl acetate or acetone and isrecrystallized from ace tone-ether giving about l.3lg. m.p. 7292C. Theinfrared spectrum confirmed the proposed structure.

Anal. Calc. C H CI N0 8: C, 61.52. H, 6.88; S. 7.82. Found: C. 61.25; H.7.25; S, 7.80.

EXAMPLE 2 a. 2-(2-Furoyl)ethyldimethylamine Hydrochloride An alcoholicsolution is prepared by refluxing on a steam bath for about 2 to 3 hoursa mixture comprising 12.0g of 2-acetylfuran. 3.9g paraformaldehyde. 8.9gdimethylamine hydrochloride. 50.0 ml absolute alcohol. and concentratedhydrochloric acid (about 4drops) with succeeding cooling to roomtemperature. Upon standing at an ambient temperature a yellow coloredprecipitate is formed which is separated by filtration and dried in avacuum oven at 50C. A yield of 9.5g. is obtained. m.p. l74-l76C.

b. 2-(2-Furoyl)ethyltrimethylammonium Iodide An alkaline solutioncomprising about 7.0g of 2-(2- Furoyl) ethyldimethylamine hydrochloride.see (a) above. in 250 ml of water is cooled in an ice bath and madebasic with about 3 ml of solution of sodium hydroxide forming animmiscible oily phase which separates out of solution. Ether extractsare prepared by treating the isolated oily phase two times with l00 mlportions and the combined extracts are dried over anhydrous sodiumsulfate. filtered and refluxed on a steam bath for about one-half hourto remove any dimethylamine. After the subsequent addition in a dropwisemanner over about a /2-hour duration of an ether solution comprisingabout 4.8g of methyl iodide in ml of sodium-dried ether resulting in asolution which is continued to reflux for an additional 1 hour duringwhich time the solution becomes cloudy. cooled overnight, an insolubleproduct is formed. separated by filtration. washed with sodium-driedether. and dried in a vacuum oven at 50C. A yield of 4.2g. m.p.l92-194C. decomposition.

c. l 2-( 2-Furoyl )ethyl ]-4-phenyl-4-piperidinol A mixture comprisingabout 3.9g of 2-(2-Furoyl)ethyltrimethylammonium iodide. see (b) above,2.2g of 4-phenyl-4-piperidinol, 2.7g sodium carbonate. and

I00 ml of dimethylformamide is stirred at room temperature with nitrogenbubbling through mixture for about 4-6 hours in order to expel theformed trimethylamine. Pouring the mixture into a liter of water formedno visible precipitate. however. upon standing overnight. a yellowproduct is formed. separated by filtration. copiously washed withdistilled water and dried overnight in vacuum oven at 60C. The yield isabout 2.1g. mp. l50153C.. recrystallization from benzene gave a m.p.l5l-l53. Infrared Spectrum confirmed the proposed structure.

Anal. Calc. c,,.H. ,.No C. 72.2; H. 7.07. Found: C. 71.6: H, 6.9.

d. l-{2-( 2-Furoyl )ethyl l-4-phenyl-4-propionoxypiperidinium ChlorideAt ambient temperature. a chloroform solution comprising about 0.4g ofpropionyl chloride in [5 ml of chloroform is added rapidly dropwise to astirring mixture comprising about 2.8g of sodium carbonate. 0.5g water,35 ml of chloroform and 1.0g ofl-[(2-Furoyl)ethyl]-4-phenyl-4-piperidinol (see (c) above) withcontinued agitation for about 4 to 6 hours. The chloroform mixturereaction product is filtered and volatiles are removed in vacuo in arotary evaporator forming an oily residue which is dissolved in ether.dried over anhy drous magnesium sulfate and filtered. The ether filtrateis cooled to about 0C. and with agitation is treated with anhydroushydrogen chloride until complete prccipitation of the hydrochloride saltwhereupon the mixture is evaporated almost to dryness in vacuo in arotary evaporator. The residue is triturated with ethyl acetate. cooledand the product is separated by filtration. Concentration of the ethylacetate filtrate produces a second crop of crystals. The product iscrystallized from acetone to give a yield of about 1.2g of the esterhydrochloride. m.p. -l 72. The proposed structure was confirmed byinfrared spectrum.

Anal. Calc. C H- ClNQz C. 64.34; H. 6.69; O. 16.33. Found: C. 63.5; H.6.7; O. 16.4.

e. l-[3-Hydroxy-3-( Z-furyl)propyl1-4-phenyl-4-propionoxypiperidiumchloride A methanolic alkaline solution about pH comprises a sodiumhydroxide pellet in 60 ml of methanol.

An approximately neutral alcoholic solution (pH 6.5 -7.5) comprisingabout l.44g of l-2[2-(Furoyl)ethyl]- 4-phenyl-4-propionoxypiperidiniumchloride (see ((1) above) in 50 ml at about 6C. of the above preparedmethanolic solution (pH l4).

Sodium borohydride 018g is dissolved in the remaining [0 ml of the aboveprepared methanolic solution. filtered and added to the above preparedsaid alcoholic solution (pH 6.5-7.5 )over 4-6 minutes maintaining thetemperature at about l0 to 20C. for about 4 to 7 hours with a subsequenttemperature rise to about 4 to 6C. The solution at the lattertemperature is treated with anhydrous hydrochloric acid with subsequentremoval of volatiles in vacuo forming a solid residue which wasextracted with ethyl acetate forming a slurry. filtered and recovering awhite residue. This latter residue is extracted with acetone and uponremoval of acetone gives about 1.2g of colored solid. mp. 143C. Thecolored solid is decolorized by redissolving in acetone and addition ofactivated carbon with re moval of the acetone forming a white product.The

7 product is recrystallized from acetone-ether gave about 0.84g of whitecrystals, m.p. l54l5S.5C. Infrared analysis confirmed the proposedstructure.

Anal. Calc. C H CI N C, 64.03; H. 7. l6; 0 16.25. Found: C. 63.8; H.7.4; O, l6.6.

EXAMPLE 3 4-Phenyl-4-propionoxy piperidium chloride (see copcndingapplication Ser. No. 648.546 for preparation) and Z-thienyl vinyl ketoneare dissolved in chloroform at room temperature resulting in theformation of l-[ 3- oxo-3-( Z-thienyl )propyl]-4-phenyl-4-propionoxypiperidium chloride.

The forms of the invention as herein given may be considered as being byway of illustration. Numerous modifications may be made therein withoutdeparture from the spirit of the invention or the scope of the appendedclaims.

I claim:

I. In a method for producing substituted piperidines l-[ 3-Oxo-3-(Z-thienyl )propyl ]-4-phenyl-4-propionoxypiperidinium chloride orl-[3-Oxo-3-(2-furyhpropyl1-4-phenyl-4-propionoxypiperidium chloridecomprising the steps of:

a. contacting 2-acetyl thiophene or Z-acetyl furan with dimethylamineand formaldehyde d. contacting the product resulting from (a) above withan excess of methyl iodide c. contacting the resulting product from (b)above with 4-phenyl-4-pipcridium chloride d. contacting the productresulting from (c) above with propionyl chloride followed anhydroushydrochloric acid and recovering l-[3-Oxo-3-(2- thienyl )propyl]-4-phenyl-4-propionoxypiperidium chloride or l-[3-Oxo-3-(2-furyl)propyl]-4-phenyl- 4-propionoxypiperidium chloride.

2. in the method according to claim 1, wherein the compound l-[3-Oxo-3-( Z-thienyl )propyl ]-4-phenyl-4- propionoxypiperidium chlorideor l-[3-Oxo-3-(2- furyl )propyl ]-4-phenyl-4-propionoxypiperidiumchloride resulting from (d) is further reacted with an alkaline loweralkyl alcohol solution and alkali metal borohydride with subsequentseparation of final product I- [3-Hydroxy- 3-( Z-thienyl )propyl]-4-phenyl-4-propionoxypiperidium chloride or l-[3-l-lydroxy-3-(2- furyl)propyl ]-4-phenyl-4-propionoxypipe ridium chloride.

3. In the method according to claim 1 wherein the acetyl compound in (a)is Z-acetyl thiophene and the product in (d) isl-[3-Oxo-3-(2-thienyl)propyl]-4-phenyl-4-propionoxypiperidium chloride.

4. In the method according to claim 1 wherein the acetyl compound in (a)is Z-acetyl furan and the product in (d) isl-[3-oxo-3-(Z-furyl)propyll-4-phenyl-4-propionoxypiperidium chloride.

5. In the method according to claim 2 wherein said compound is l-[3-Oxo-3-( Z-thienyl )propyll-4-phenyl- 4-propionoxypiperidium chlorideand said product is l-[ 3-Hydroxy-3-( 2-thie nyl )propyll-4-phenyl-4-propionoxypiperidium chloride.

6. In the method according to claim 2 wherein said compound is l-[3-Oxo-3-( 2-furyl )propyl]-4-phenyl-4- propionoxypiperidium chloride andsaid product is [3-Hydroxy-3-(Z-furyl)propyl1-4-phenyl-4-propionoxypiperidium chloride.

7. A method of preparing l-[3-Oxo-3-(2-thienyl)-propyl]-4-phenyl-4-propionoxypiperidium chloride the steps comprisingreacting 4-phenyl-4-propionoxypiperidium chloride and 2-thienyl vinylketone in chloroform producing l-[ 3-Oxo-3-( Z-thienyl )eropyl4-phenyl-4-propionoxypiperidium chloride.

8. The compound RQZ- N ()CO H HCl wherein R is 2-thienyl or Z-furyl. Qis carbonyl or and Z is lower alkylene.

9. The compound 1-[3-Hydroxy-3-(2-thienyl)- propyl -4-phenyl-4-propionoxypiperidium Chloride.

10. The compound l-[3-Oxo-3-(2-thienyl)propyl1-4- phenyl-4propion0xypiperidium Chloride.

11. The compound l-[3-Hydroxy-3-(2-furyl )propyl]-4-phenyl-4-propionoxypiperidium chloride.

12. The compound l-[3-Oxo-3-(2-furyl)propyl]-4-phenyl-4-propionoxypiperidium chloride.

1. IN A METHOD FOR PRODUCING SUBSTITUTED PIPERIDINES1-(3OXO-3-(2-DTHIENYL) PROPYL) -4- PHENYL -4- PROPIONOX YPIPERIDINIUMCHLORIDE OR 1-(3-OXO-3(2-FURY)PROPYLE-4-PHENYL-4-PROPIONOXYPIPERIDIUMCHLORIDE COMPRISING THE STEPS OF A.CONTACTING 2-ACETYL THIOPHENE OR2-ACETYL FURAN WITH DIMETHYLAMINE AND FORMALDEHYDE D.CONTACTING THEPRODUCT RESULTING FROM (A) ABOVE WITH AN EXCESS OF METHYL IODINE C.CONTACTING THE RESULTING PRODUCT FROM (B) ABOVE WITH4PHENYL-4-PIPERIDIUM CHLORIDE D.CONTACTING THE PRODUCT RESULTING FROM(C) ABOVE WITH PROPIONYL CHLORIDE FOLLOWED ANHYDROUS HYDROCHLORIC ACIDAND RECOVERING 1-(3-OX-3-(2-THIENYL)PROPYL)-J-PHENYL4-PROPRONOXYPIPERIDIUM CHLORIDE OR1-(3-OXO-3-(2FURY)PROPYL-4-PHENYL-4-PROPIONOXYPIPERIDIUM CHLORIDE.
 2. Inthe method according to claim 1, wherein the compound1-(3-Oxo-3-(2-thienyl)propyl)-4-phenyl-4-propionoxypiperidium chlorideor 1-(3-Oxo-3-(2-furyl)propyl)-4-phenyl-4-propionoxypiperidium chlorideresulting from (d) is further reacted with an alkaline lower alkylalcohol solution and alkali metal borohydride with subsequent separationof final product1-(3-Hydroxy-3-(2-thienyl)propyl)-4-phenyl-4-propionoxypiperidiumchloride or1-(3-Hydroxy-3-(2-furyl)propyl)-4-phenyl-4-propionoxypiperidiumchloride.
 3. In the method according to claim 1 wherein the acetylcompound in (a) is 2-acetyl thiophene and the product in (d) is1-(3-Oxo-3-(2-thienyl)propyl)-4-phenyl-4-propionoxypiperidium chloride.4. In the method according to claim 1 wherein the acetyl compound in (a)is 2-acetyl furan and the product in (d) is1-(3-oxo-3-(2-furyl)propyl)-4-phenyl-4-propionoxypiperidium chloride. 5.In the method according to claim 2 wherein said compound is1-(3-Oxo-3-(2-thienyl)propyl)-4-phenyl-4-propionoxypiperidium chlorideand said product is1-(3-Hydroxy-3-(2-thienyl)propyl)-4-phenyl-4-propionoxypiperidiumchloride.
 6. In the method according to claim 2 wherein said compound is1-(3-Oxo-3-(2-furyl)propyl)-4-phenyl-4-propionoxypiperidium chloride andsaid product is1-(3-Hydroxy-3-(2-furyl)propyl)-4-phenyl-4-propionoxypiperidiumchloride.
 7. A method of preparing1-(3-Oxo-3-(2-thienyl)propyl)-4-phenyl-4-propionoxypiperidium chloridethe steps comprising reacting 4-phenyl-4-propionoxypiperidium chlorideand 2-thienyl vinyl ketone in chloroform producing1-(3-Oxo-3-(2-thienyl)eropyl)-4-phenyl-4-propionoxypiperidium chloride.8. The compound
 9. The compound1-(3-Hydroxy-3-(2-thienyl)propyl)-4-phenyl-4-propionoxypiperidiumChloride.
 10. The compound1-(3-Oxo-3-(2-thienyl)propyl)-4-phenyl-4propionoxypipe ridium Chloride.11. The compound1-(3-Hydroxy-3-(2-furyl)propyl)-4-phenyl-4-propionoxypiperidiumchloride.
 12. The compound1-(3-Oxo-3-(2-furyl)propyl)-4-phenyl-4-propionoxypiperidium chloride.